Mechanisms of interactions of complement, immunoglobulin and Factor VIII with the human platelet will be explored and interrelationships defined. The human platelet activity which initiates formation of the C5-9 complex of human complement will be isolated and characterized by functional, physicochemical and immunological criteria and compared with platelet Factor VIII activating activity. The requirements for other plasma proteins in platelet initiated C5-9 formation will be defined and the incorporation of platelet proteins within the C5-9 complex explored. Structural requirements for immunoglobulin platelet interaction will be determined utilizing fragments of the normal immunoglobulin molecule and a myeloma protein deficient in the C gamma 3 domain. Structural modification known to effect interaction of immunoglobulins and Factor VIII with the platelet will be compared. The platelet Fc receptor will be isolated, characterized,and compared with that for Factor VIII. Platelet Factor VIII related antigen (VIIIAg) will be isolated, characterized by physicochemical and immunologic criteria, and compared with plasma VIII Ag forms. The relative importance of the different plasma VIII Ag forms to platelet function will be determined. The effect of the platelet on the physicochemical and immunologic characteristics of the specific plasma VIII Ag forms will be determined and compared to the effects of thrombin, plasmin, and other enzymes. Immunologic assays specific for the different platelet VIII Ag forms will be used to define the relative contribution of these forms to plasma VIII Ag changes occurring in different physiologic and pathologic states.